Without limiting the scope of the invention, its background is described in connection with novel methods and apparatus for modulation of autonomic system control of muscle activity. The autonomic nervous system controls many vital bodily systems, including the cardiovascular system, gastrointestinal, urinary and bowel functions, temperature regulation, and muscle tone.
The autonomic nervous system is primarily composed of the sympathetic and parasympathetic systems. In certain diseases and conditions, the balance between sympathetic and parasympathetic system control is implicated either causally or in attempted remediation. For example, filling and emptying of the bladder, or “reflex micturition”, involves a balance of sympathetic and parasympathetic control. Filling of the bladder requires relaxation of the detrusor muscle of the bladder due to sympathetic stimulation of beta-adrenergic receptors as well as sympathetic stimulation of alpha-adrenegic receptors by norepinephrine causing contraction of the internal involuntary urethral sphincter of the bladder neck.
Conversely, emptying of the bladder is effected when the cortical center of the brain triggers inhibition of sympathetic impulses and stimulates the parasympathetic system to release acetylcholine which results in relaxation of the internal and external sphincters and contraction of the detrusor muscle. Changes to the physiology of the urinary tract as a consequence of aging and which affect continence include decreases in bladder elasticity with reduced bladder capacity resulting in more frequent urination and decrease in strength of the detrusor muscle, resulting in incomplete emptying.
Reflex micturition is implicated in Lower Urinary Tract Symptoms (LUTS), including those caused by prostatic enlargement or Benign Prostatic Hyperplasia (BPH). LUTS is quite common in men as they age. In one study of men aged 40-80, 54% needed to wake up at least once at night to urinate, 47% indicated they had terminal dribbling sometimes or frequently, 30% experienced urgency (although only 4% had urge incontinence), 21% experienced hesitancy, and 19% could retain urine in their bladder during the day for no more than 2 hours. Sladden M J et al. A Community Study of Lower Urinary Tract Symptoms in Older Men in Syndey, Australia, ANZ Journal of Surgery, May 2000, vol. 70, no. 5, pp. 322-328(7).
BPH is the most common benign neoplasm in men and can be identified histologically in half of all men at age 60, and in 90% by 85 years. The increase in size of the prostate inside its capsule exerts pressure on the urethra, which passes through the capsule, resulting in obstruction to urine flow. As the prostate enlarges, the gland is forced to press against the urethra in a clamp-like fashion. The bladder wall becomes thicker and irritable and is less extensible thus reducing capacity. The bladder can contract even when it contains small amounts of urine resulting in frequent urination. Ultimately, the bladder weakens and loses the ability to fully empty. Urine retention and strain on the bladder can lead to urinary tract infections, bladder or kidney damage, bladder stones, and incontinence. In the USA, about 25% of men will be treated for BPH by age 80, and over 300,000 surgical procedures are performed each year for BPH (mostly transurethral resection of the prostate, TURP).
In certain cases of hesitancy where the prostate is not significantly enlarged (no prostate disease), excessive sympathetic tone (due to anxiety and other factors) is present. One social anxiety syndrome resulting in inability to relax the urinary sphincter muscles is “paruresis” (a.k.a. shy bladder syndrome, bashful bladder syndrome (BBS), bashful kidneys, pee-phobia, urophobia, and psychogenic urinary retention) is characterized by difficulty in urinating in the presence of others. Individuals with BBS are sometimes referred to as paruretics. This syndrome may affect as much as seven percent (7%) of the US public, or 17 million people, both male and female, and affected individuals may be required to utilize self-catheterization in order to empty the bladder.
In individuals having hesitancy due to excessive sympathetic tone, diminishing the activity of the sympathetic nervous system by α-adrenoreceptor antagonists (alpha blockers) is helpful in treatment. The alpha blocker drugs aim at reducing sympathetic tone of the bladder particularly the neck of bladder. It can also help people with enlarged prostate in whom relaxing the tone of the neck can be useful. Alpha blockers that have been approved for the treatment of symptoms associated with BHP include the drugs terazosin (marketed as Hytrin), doxazosin (marketed as Cardura), tamsulosin (marketed as Flomax), and alfuzosin (marketed as Uroxatral). All of these drugs act to by relaxing the smooth muscle of the prostate and bladder neck to improve urine flow and to reduce bladder outlet obstruction. Terazosin and doxazosin were developed first to treat high blood pressure, while tamsulosin and alfuzosin were developed specifically to treat BPH. The problem with use of alpha blockers is that the entire body is treated to ameliorate a local condition. Each of these drugs can have use limiting side effects.
What is needed are methods and apparatus for modulating the balance between the sympathetic and parasympathetic components of the autonomic nervous system in the treatment of a number of conditions including inducing a rapid anti-sympathetic effect that lasts only long enough alleviate conditions manifest by excessive sympathetic tone, including conditions such as hesitancy during urination and shy bladder.